Tremorogenesis by physostigmine is unrelated to acetylcholinesterase inhibition: evidence for serotoninergic involvement.
Studies were performed to bring out a serotoninergic involvement in physostigmine tremor, hitherto known to be working via the cholinergic system. 5-Hydroxytryptamine (5-HT) was estimated fluorimetrically after isolation on Sephadex G-10 and acetylcholinesterase (AChE) was assayed spectrophotometrically. The dose-dependent tremor was quantified by a double-blind study. No correlation (r = 0.01) existed between tremor and AChE inhibition since the non-tremoring dose of physostigmine caused the same degree of enzyme inhibition. An increase of 5-HT was found to be correlated (r = 0.59) with the duration and intensity of tremor. Cholinergic antagonists atropine (2 and 5 mg/kg, i.p.), scopolamine (0.5, 1.0, 2.0 mg/kg, i.p.) and mecamylamine (1 mg/kg, i.p.) failed to block the tremor while the 5-HT antagonists methysergide (5 mg/kg, i.v.) and cyproheptadine (10 and 30 mg/kg, s.c.) could afford more than 60% protection. These results suggest a serotoninergic rather than a cholinergic component in the genesis of physostigmine tremor.
Mohanakumar
K P
KP
Division of Pharmacology and Experimental Therapeutics, Indian Institute of Chemical Biology, Calcutta.
Mitra
N
N
Ganguly
D K
DK
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002421:Caudate Nucleus / Q000187:drug effects / Q000201:enzymology*; D003533:Cyproheptadine / Q000494:pharmacology; D008464:Mecamylamine / Q000494:pharmacology; D008636:Mesencephalon / Q000187:drug effects / Q000201:enzymology*; D008784:Methysergide / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011699:Putamen / Q000187:drug effects / Q000201:enzymology*; D012601:Scopolamine / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology*; D014202:Tremor / Q000139:chemically induced / Q000503:physiopathology*
C026718:physostigmine salicylate; D003533:Cyproheptadine; D012701:Serotonin; D008464:Mecamylamine; D001285:Atropine; D010830:Physostigmine; D012601:Scopolamine; D000110:Acetylcholinesterase; D008784:Methysergide